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2017-11-07 - Article/Dans un journal avec peer-review - Anglais - 19 page(s)

Andre Séverine , Ansciaux Emilie, Saidi Elamine, Larbanoix Lionel , Stanicki Dimitri , Nonclercq Denis , Vander Elst Luce , Laurent Sophie , Muller Robert , Burtea Carmen , "Validation by magnetic resonance imaging of the diagnostic potential of a heptapeptide-functionalized imaging probe targeted to amyloid beta and able to cross the blood-brain barrier" in Journal of Alzheimer's Disease, 60, 4, 1547-1565, 10.3233/JAD-170563

  • Edition : IOS Press (Netherlands)
  • Codes CREF : Histologie (DI3212), Sciences biomédicales (DI3200), Biochimie pharmaceutique (DI3491), Biologie moléculaire (DI3111), Neuropathologie (DI332C), Biologie cellulaire (DI311D)
  • Unités de recherche UMONS : Chimie générale, organique et biomédicale (M108), Histologie (M118)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé), Institut des Biosciences (Biosciences)
  • Centres UMONS : Centre de Recherche en Microscopie et Imagerie Médicale (CMMI)
Texte intégral :

Abstract(s) :

(Anglais) The diagnosis of Alzheimer’s disease (AD) is a critical step in the management of patients. We have developed a non-invasive diagnosis tool based on magnetic resonance molecular imaging (MRMI) of amyloid-peptide using ultrasmall particles of iron oxide (USPIO) functionalized with a disulfide constrained cyclic heptapeptide (PHO) identified by phage display (USPIO-PHO). After previously demonstrating the optimal pharmacologic properties of USPIO-PHO and its capacity to cross the blood-brain barrier (BBB), the ability of USPIO-PHO to target amyloid plaques (AP) by MRMI has been validated in the present work on AD transgenic mice. The immunohistochemistry and immunofluorescent detection of USPIO-PHO on brain sections collected after in vivo MRMI studies enabled its colocalization with AP, confirming the BBB passage and specific targeting. The AP targeting by USPIO-PHO has been moreover corroborated by the good correlation between the number of AP detected with anti-amyloid antibody and Perls’-DAB staining. Finally, the crossing mechanism of USPIO-PHO through the BBB was elucidated, revealing the involvement of non-degradation pathway of caveolae, while the control contrast agent USPIO-PEG was not endocytosed by the human brain endothelial cells.

(Anglais) The diagnosis of Alzheimer’s disease (AD) is a critical step in the management of patients. We have developed a non-invasive diagnosis tool based on magnetic resonance molecular imaging (MRMI) of amyloid-beta peptide using ultrasmall particles of iron oxide (USPIO) functionalized with a disulfide constrained cyclic heptapeptide (PHO) identified by phage display (USPIO-PHO). After previously demonstrating the optimal pharmacologic properties of USPIO-PHO and its capacity to cross the blood-brain barrier (BBB), the ability of USPIO-PHO to target amyloid plaques (AP) by MRMI has been validated in the present work on AD transgenic mice. The immunohistochemistry and immunofluorescent detection of USPIO-PHO on brain sections collected after in vivo MRMI studies enabled its colocalization with AP, confirming the BBB passage and specific targeting. The AP targeting by USPIO-PHO has been moreover corroborated by the good correlation between the number of AP detected with anti-amyloid antibody and Perls’-DAB staining. Finally, the crossing mechanism of USPIO-PHO through the BBB was elucidated, revealing the involvement of non-degradation pathway of caveolae, while the control contrast agent USPIO-PEG was not endocytosed by the human brain endothelial cells.

(Anglais) The diagnosis of Alzheimer’s disease (AD) is a critical step in the management of patients. We have developed a non-invasive diagnosis tool based on magnetic resonance molecular imaging (MRMI) of amyloid-peptide using ultrasmall particles of iron oxide (USPIO) functionalized with a disulfide constrained cyclic heptapeptide (PHO) identified by phage display (USPIO-PHO). After previously demonstrating the optimal pharmacologic properties of USPIO-PHO and its capacity to cross the blood-brain barrier (BBB), the ability of USPIO-PHO to target amyloid plaques (AP) by MRMI has been validated in the present work on AD transgenic mice. The immunohistochemistry and immunofluorescent detection of USPIO-PHO on brain sections collected after in vivo MRMI studies enabled its colocalization with AP, confirming the BBB passage and specific targeting. The AP targeting by USPIO-PHO has been moreover corroborated by the good correlation between the number of AP detected with anti-amyloid antibody and Perls’-DAB staining. Finally, the crossing mechanism of USPIO-PHO through the BBB was elucidated, revealing the involvement of non-degradation pathway of caveolae, while the control contrast agent USPIO-PEG was not endocytosed by the human brain endothelial cells.

(Anglais) The diagnosis of Alzheimer’s disease (AD) is a critical step in the management of patients. We have developed a non-invasive diagnosis tool based on magnetic resonance molecular imaging (MRMI) of amyloid-beta peptide using ultrasmall particles of iron oxide (USPIO) functionalized with a disulfide constrained cyclic heptapeptide (PHO) identified by phage display (USPIO-PHO). After previously demonstrating the optimal pharmacologic properties of USPIO-PHO and its capacity to cross the blood-brain barrier (BBB), the ability of USPIO-PHO to target amyloid plaques (AP) by MRMI has been validated in the present work on AD transgenic mice. The immunohistochemistry and immunofluorescent detection of USPIO-PHO on brain sections collected after in vivo MRMI studies enabled its colocalization with AP, confirming the BBB passage and specific targeting. The AP targeting by USPIO-PHO has been moreover corroborated by the good correlation between the number of AP detected with anti-amyloid beta antibody and Perls’-DAB staining. Finally, the crossing mechanism of USPIO-PHO through the BBB was elucidated, revealing the involvement of non-degradation pathway of caveolae, while the control contrast agent USPIO-PEG was not endocytosed by the human brain endothelial cells.